Pyruvate dehydrogenase kinase (PDK) is a mitochondrial protein that controls energy flux through the mammalian cell by modulating the activity of the large mitochondrial pyruvate dehydrogenase complex. Crystals have been obtained of active, recombinant mammalian material and native data has been collected to 2.5 E. However, PDK is a novel kinase, with virtually no sequence identity with the well characterized cytoplasmic protein kinases. Phasing experiments are underway, utilizing both traditional isomorphous replacement, and selenomethionine techniques. The ultimate goal of the project is to develop a three dimensional structural model of PDK that can serve as the basis for further exploration of its activity, as well as the starting point for a structure directed inhibitor design program.